1. Field of the Invention
This invention relates to a novel dipeptide derivative and a prophylactic and therapeutic agent for bone diseases containing the same as an active ingredient.
2. Prior Art
In recent years, the rapid increase in the number of aged people in the population has caused an increase of so-called geriatric diseases. Among these diseases, bone diseases including osteoporosis are accompanied by a higher incidence of bone fracture, and this has been the major cause of the increase of aged patients who are bed-ridden. Therefore it is urgently required to develop a method for preventing and treating the above-mentioned bone diseases.
Bone is not a tissue which does not undergo any change once formed. It is continuously formed and metabolized. Thus the structure and amount of bone is maintained due to the balance between osteogenesis and bone resorption. When this balance is lost due to aging or some other factors, various bone diseases are induced. Examples of diseases due to sthenic bone resorption include malignant hypercalcemia caused by myeloma or lymphoma, bone Paget's disease caused by local bone resorption and osteoporosis in aged people accompanied by decrease in bone weight, though the etiological causes of this disease are as yet unknown.
Bones mainly comprise collagen fibers (i.e., organic matter) and calcium salts (i.e., inorganic matter). These substances are combined to form bones, constructions which are highly resistant against tension and pressure. In particular, calcium salts amount to 70% of the total bone weight. As bone diseases proceed, calcium salts tend to dissolve into the blood and thus are slowly lost.
Known methods for .preventing or treating these diseases comprise supplying calcium or maintaining the normal calcium level, and in this context active vitamin D.sub.3 preparations and calcium preparations have been employed. Further, hormone preparations, such as estrogen preparations and calcitonin preparations, have been used in order to suppress decalcification of bones.
In addition to the above-mentioned therapeutic methods for preventing a decrease of calcium salts, importance of preventing a decrease of collagen fibers in bone diseases has been recently noted. Namely, studies have been conducted to elucidate enzymes decomposing collagen fiber present as a matrix of bones in an attempt to develop an inhibitor of such enzymes for use in the treatment of bone resorption diseases (see Japanese Patent Laid-Open Nos. 284127/1988 and 218619/1990). However, these studies have just been initiated, and it is only but yesterday that collagen type I, which is the collagen contained in bones as the matrix, was found to be decomposed by cathepsin L which is a thiol protease found among lysosomal enzymes [see Nobuhiko Katsunuma, Gakushikai Kaiho, No. 792, 48-53 (1991)]. No clinical cases where patients were cured by using an inhibitor of a collagen decomposing enzyme have been reported, and no practical therapeutic agent of this type has been provided so far.